Amebiasis is estimated to cause 100,000 deaths annually. This is a competing renewal application for an NIH grant that has supported a community-based prospective study of Entamoeba histolytica infection in preschool children from Bangladesh. The study has yielded two important findings: (1) Acquired immunity to E. histolytica infection exists. Children with an intestinal secretory IgA directed against the E. histolytica Gal/GalNAc lectin carbohydrate recognition domain (CRD) have an 86% reduction in new infections at one year of follow-up. (2) Amebiasis is an important cause of preschool childhood morbidity in Mirpur. Most (55%) of the preschool children have been infected with E. histolytica, and 4.3% have had amebic dysentery. We propose to build on these initial observations through continued prospective study of the children. Specific Aim 1 will test the hypothesis that the incidence of E. histolytica infection will increase in the children as they enter grade school ages. Specific Aim 2 will discover whether immunity to E. histolytica infection is long lasting. Specific Aim 3 will test if acquired immunity is associated not only with mucosal anti-CRD IgA, but also with cell-mediated immune responses that produce interferon gamma, tumor necrosis factor alpha, and/or nitric oxide. Additionally because class W-restricted immune responses are likely to play important roles in immunity, Aim 3 will test if specific HLA class II alleles are associated with the ability to mount an effective acquired immune response. Successful completion of these studies will aid in design of an amebiasis vaccine and should provide insight into the immunology of host-parasite interactions at mucosal surfaces.